Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system

ABSTRACT

Buccal aerosol sprays or capsules using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprise formulation I: aqueous polar solvent, active compound, and optional flavoring agent; formulation II: aqueous polar solvent, active compound, optionally flavoring agent, and propellant; formulation III: non-polar solvent, active compound, and optional flavoring agent; and formulation IV: non-polar solvent, active compound, optional flavoring agent, and propellant.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of application Ser.No. 09/537,118, filed Mar. 29, 2000 which is a continuation-in-part ofthe U.S. national phase designation of PCT/US97/17899 filed Oct. 1,1997, the disclosures of which are incorporated by reference herein intheir entirety.

BACKGROUND OF THE INVENTION

[0002] It is known that certain biologically active compounds are betterabsorbed through the oral mucosa than through other routes ofadministration, such as through the stomach or intestine. However,formulations suitable for such administration by these latter routespresent their own problems. For example, the biologically activecompound must be compatible with the other components of the compositionsuch as propellants, solvents, etc. Many such formulations have beenproposed. For example, U.S. Pat. No. 4,689,233, Dvorsky et al.,describes a soft gelatin capsule for the administration of theanti-coronary drug nifedipine dissolved in a mixture of polyetheralcohols. U.S. Pat. No. 4,755,389, Jones et al., describes a hardgelatin chewable capsule containing nifedipine. A chewable gelatincapsule containing a solution or dispersion of a drug is described inU.S. Pat. No. 4,935,243, Borkan et al. U.S. Pat. No. 4,919,919, Aouda etal, and U.S. Pat. No. 5,370,862, Klokkers-Bethke, describe anitroglycerin spray for administration to the oral mucosa comprisingnitroglycerin, ethanol, and other components. An orally administeredpump spray is described by Cholcha in U.S. Pat. No. 5,186,925. Aerosolcompositions containing a hydrocarbon propellant and a drug foradministration to a mucosal surface are described in U.K. 2,082,457, Su,U.S. Pat. No. 3,155,574, Silson et al., U.S. Pat. No. 5,011,678, Wang etal., and by Parnell in U.S. Pat. No. 5,128,132. It should be noted thatthese references discuss bioavailability of solutions by inhalationrather than through the membranes to which they are administered.

SUMMARY OF THE INVENTION

[0003] A buccal aerosol spray or soft bite gelatin capsule using a polaror non-polar solvent has now been developed which provides biologicallyactive compounds for rapid absorption through the oral mucosa, resultingin fast onset of effect.

[0004] The buccal aerosol spray compositions of the present invention,for transmucosal administration of a pharmacologically active compoundsoluble in a pharmacologically acceptable non-polar solvent comprise inweight % of total composition: pharmaceutically acceptable propellant5-80%, nonpolar solvent 19-85%, active compound 0.05-50%, suitablyadditionally comprising, by weight of total composition a flavoringagent 0.01-10%. Preferably the composition comprises: propellant 10-70%,non-polar solvent 25-89.9%, active compound 0.01-40%, flavoring agent1-8%; most suitably propellant 20-70%, non-polar solvent 25-74.75%,active compound 0.25-35%, flavoring agent 2-7.5%.

[0005] The buccal polar aerosol spray compositions of the presentinvention, for transmucosal administration of a pharmacologically activecompound soluble in a pharmacologically acceptable polar solvent arealso administrable in aerosol form driven by a propellant. In this case,the composition comprises in weight % of total composition: aqueouspolar solvent 10-97%, active compound 0.1-25%, suitably additionallycomprising, by weight of total composition a flavoring agent 0.05-10%and propellant: 2-10%. Preferably the composition comprises: polarsolvent 20-97%, active compound 0.1-15%, flavoring agent 0.1-5% andpropellant 2-5%; most suitably polar solvent 25-97%, active compound0.2-25%, flavoring agent 0.1-2.5% and propellant 2-4%.

[0006] The buccal pump spray composition of the present invention, i.e.,the propellant free composition, for transmucosal administration of apharmacologically active compound wherein said active compound issoluble in a pharmacologically acceptable non-polar solvent comprises inweight % of total composition: non-polar solvent 30-99.69%, activecompound 0.005-55%, and suitably additionally, flavoring agent 0.1-10%.

[0007] The buccal polar pump spray compositions of the presentinvention, i.e., the propellant free composition, for transmucosaladministration of a pharmacologically active compound soluble in apharmacologically acceptable polar solvent comprises in weight % oftotal composition: aqueous polar solvent 30-99.69%, active compound0.001-60%, suitably additionally comprising, by weight of totalcomposition a flavoring agent 0.1-10%. Preferably the compositioncomprises: polar solvent 37-98.58%, active compound 0.005-55%, flavoringagent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound0.01-40%, flavoring agent 0.75-7.5%.

[0008] The soft bite gelatin capsules of the present invention fortransmucosal administration of a pharmacologically active compound, atleast partially soluble in a pharmacologically acceptable non-polarsolvent, having charged thereto a fill composition comprise in weight %of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%,active compound 0.01-80%, provided that said fill composition containsless than 10% of water, suitably additionally comprising, by weight ofthe composition: flavoring agent 0.01-10%. Preferably, the soft bitegelatin capsule comprises: non-polar solvent 21.5-99.975%, emulsifier0-15%, active compound 0.025-70%, flavoring agent 1-8%; most suitably:nonpolar solvent 28.5-97.9%, emulsifier 0-10%, active compound0.1-65.0%, flavoring agent 2-6%.

[0009] The soft bite polar gelatin capsules of the present invention fortransmucosal administration of a pharmacologically active compound, atleast partially soluble in a pharmacologically acceptable polar solvent,having charged thereto a composition comprising in weight % of totalcomposition: polar solvent 25-99.89%, emulsifier 0-20%, active compound0.01-65%, provided that said composition contains less than 10% ofwater, suitably additionally comprising, by weight of the composition:flavoring agent 01-10%. Preferably, the soft bite gelatin capsulecomprises: polar solvent 37-99.95%, emulsifier 0-15%, active compound0.025-55%, flavoring agent 1-8%; most suitably: polar solvent44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent2-6%.

[0010] It is an object of the invention to coat the mucosal membraneseither with extremely fine droplets of spray containing the activecompounds or a solution or paste thereof from bite capsules.

[0011] It is also an object of the invention to administer to the oralmucosa of a mammalian in need of same, preferably man, by spray or bitecapsule, a predetermined amount of a biologically active compound bythis method or from a soft gelatin capsule.

[0012] A further object is a sealed aerosol spray container containing acomposition of the non polar or polar aerosol spray formulation, and ametered valve suitable for releasing from said container a predeterminedamount of said composition.

[0013] As the propellant evaporates after activation of the aerosolvalve, a mist of fine droplets is formed which contains solvent andactive compound.

[0014] The propellant is a non-Freon material, preferably a C₃₋₈hydrocarbon of a linear or branched configuration. The propellant shouldbe substantially non-aqueous. The propellant produces a pressure in theaerosol container such that under expected normal usage it will producesufficient pressure to expel the solvent from the container when thevalve is activated but not excessive pressure such as to damage thecontainer or valve seals.

[0015] The non-polar solvent is a non-polar hydrocarbon, preferably aC₇₋₁₈ hydrocarbon of a linear or branched configuration, fatty acidesters, and triglycerides, such as miglyol. The solvent must dissolvethe active compound and be miscible with the propellant, i.e., solventand propellant must form a single phase at a temperature of 0-40° C. apressure range of between 1-3 atm.

[0016] The polar and non-polar aerosol spray compositions of theinvention are intended to be administered from a sealed, pressurizedcontainer. Unlike a pump spray, which allows the entry of air into thecontainer after every activation, the aerosol container of the inventionis sealed at the time of manufacture. The contents of the container arereleased by activation of a metered valve, which does not allow entry ofatmospheric gasses with each activation. Such containers arecommercially available.

[0017] A further object is a pump spray container containing acomposition of the pump spray formulation, and a metered valve suitablefor releasing from said container a predetermined amount of saidcomposition.

[0018] A further object is a soft gelatin bite capsule containing acomposition of as set forth above. The formulation may be in the form ofa viscous solution or paste containing the active compounds. Althoughsolutions are preferred, paste fills may also be used where the activecompound is not soluble or only partially soluble in the solvent ofchoice. Where water is used to form part of the paste composition, itshould not exceed 10% thereof. (All percentages herein are by weightunless otherwise indicated.)

[0019] The polar or non-polar solvent is chosen such that it iscompatible with the gelatin shell and the active compound. The solventpreferably dissolves the active compound. However, other componentswherein the active compound is not soluble or only slightly soluble maybe used and will form a paste fill.

[0020] Soft gelatin capsules are well known in the art. See, forexample, U.S. Pat. No. 4,935,243, Borkan et al., for its teaching ofsuch capsules. The capsules of the present invention are intended to bebitten into to release the low viscosity solution or paste therein,which will then coat the buccal mucosa with the active compounds.Typical capsules, which are swallowed whole or bitten and thenswallowed, deliver the active compounds to the stomach, which results insignificant lag time before maximum blood levels can be achieved orsubject the compound to a large first pass effect. Because of theenhanced absorption of the compounds through the oral mucosa and nochance of a first pass effect, use of the bite capsules of the inventionwill eliminate much of the lag time, resulting in hastened onset ofbiological effect. The shell of a soft gelatin capsule of the inventionmay comprise, for example: gelatin: 50-75%, glycerin 20-30%, colorants0.5-1.5%, water 5-10%, and sorbitol 2-10%.

[0021] The active compound may include, biologically active peptides,central nervous system active amines, sulfonyl ureas, antibiotics,antifungals, antivirals, sleep inducers, antiasthmatics, bronchialdilators, antiemetics, histamine H-2 receptor antagonists, barbiturates,prostaglandins and neutraceuticals.

[0022] The active compounds may also include antihistamines, alkaloids,hormones, benzodiazepines and narcotic analgesics. While not limitedthereto, these active compounds are particularly suitable for non-polarpump spray formulation and application.

[0023] The active compounds may also include p-FOX (fatty acidoxidation) inhibitors, acetylcholinesterase inhibitors, nerve impulseinhibitors, anti-cholinergics, anti-convulsants, anti-psychotics,anxiolytic agents, dopamine metabolism inhibitors, agents to treat poststroke sequelae, neuroprotectants, agents to treat Alzheimer's disease,neurotransmitters, neurotransmitter agonists, sedatives, agents fortreating attention deficit disorder, agents for treating narcolepsy,central adregenic antagonists, anti-depression agents, agents fortreating Parkinson's disease, benzodiazepine antagonists, stimulants,neurotransmitter antagonists, tranquilizers, or a mixture thereof.

BRIEF DESCRIPTION OF THE DRAWING

[0024]FIG. 1. is a schematic diagram showing routes of absorption andprocessing of pharmacologically active substances in a mammalian system.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] The preferred active compounds of the present invention are in anionized, salt form or as the free base of the pharmaceuticallyacceptable salts thereof (provided, for the aerosol or pump spraycompositions, they are soluble in the spray solvent). These compoundsare soluble in the non-polar solvents of the invention at usefulconcentrations or can be prepared as pastes at useful concentrations.These concentrations may be less than the standard accepted dose forthese compounds since there is enhanced absorption of the compoundsthrough the oral mucosa. This aspect of the invention is especiallyimportant when there is a large (40-99.99%) first pass effect.

[0026] As propellants for the non polar sprays, propane, N-butane,iso-butane, N-pentane, iso-pentane, and neo-pentane, and mixturesthereof may be used. N-butane and iso-butane, as single gases, are thepreferred propellants. It is permissible for the propellant to have awater content of no more than 0.2%, typically 0.1-0.2%. All percentagesherein are by weight unless otherwise indicated. It is also preferablethat the propellant be synthetically produced to minimize the presenceof contaminants which are harmful to the active compounds. Thesecontaminants include oxidizing agents, reducing agents, Lewis acids orbases, and water. The concentration of each of these should be less than0.1%, except that water may be as high as 0.2%.

[0027] Suitable non-polar solvents for the capsules and the non-polarsprays include (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbon,C₂-C₆ alkanoyl esters, and the triglycerides of the corresponding acids.When the capsule fill is a paste, other liquid components may be usedinstead of the above low molecular weight solvents. These include soyaoil, corn oil, other vegetable oils.

[0028] As solvents for the polar capsules or sprays there may be usedlow molecular weight polyethyleneglycols (PEG) of 400-1000 Mw(preferably 400-600), low molecular weight (C₂-C₈) mono and polyols andalcohols of C₇-C₁₈ linear or branch chain hydrocarbons, glycerin mayalso be present and water may also be used in the sprays, but only inlimited amount in the capsules.

[0029] It is expected that some glycerin and water used to make thegelatin shell will migrate from the shell to the fill during the curingof the shell. Likewise, there may be some migration of components fromthe fill to the shell during curing and even throughout the shelf-lifeof the capsule.

[0030] Therefore, the values given herein are for the compositions asprepared, it being within the scope of the invention that minorvariations will occur.

[0031] The preferred flavoring agents are synthetic or natural oil ofpeppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners(sugars, aspartame, saccharin, etc.), and combinations thereof.

[0032] The active substances include the active compounds selected fromthe group consisting of cyclosporine, sermorelin, octreotide acetate,calcitonin-salmon, insulin lispro, sumatriptan succinate, clozepine,cyclobenzaprine, dexfenfluramine hydrochloride, glyburide, zidovudine,erythromycin, ciprofloxacin, ondansetron hydrochloride, dimenhydrinate,cimetidine hydrochloride, famotidine, phenytoin sodium, phenytoin,carboprost thromethamine, carboprost, diphenhydramine hydrochloride,isoproterenol hydrochloride, terbutaline sulfate, terbutaline,theophylline, albuterol sulfate and neutraceuticals, that is to saynutrients with pharmacological action such as but not limited tocarnitine, valerian, echinacea, and the like.

[0033] In another embodiment, the active compound is a p-FOX (fatty acidoxidation) inhibitor, acetylcholinesterase inhibitor, nerve impulseinhibitor, anti-cholinergic, anti-convulsant, anti-psychotic, anxiolyticagent, dopamine metabolism inhibitor, agent to treat post strokesequelae, neuroprotectant, agent to treat Alzheimer's disease,neurotransmitter, neurotransmitter agonist, sedative, agent for treatingattention deficit disorder, agent for treating narcolepsy, centraladregenic antagonist, anti-depression agent, agent for treatingParkinson's disease, benzodiazepine antagonist, stimulant,neurotransmitter antagonist, tranquilizer, or a mixture thereof.

[0034] In one embodiment the active compound is a p-FOX inhibitor. Asuitable p-FOX inhibitor for use in the buccal sprays of the inventionincludes, but is not limited to, ranolazine.

[0035] In one embodiment the active compound is an acetylcholinesteraseinhibitor. Suitable acetylcholinesterase inhibitors for use in thebuccal sprays of the invention include, but are not limited to,galantamine, neostigmine, physostigmine, and edrophonium.

[0036] In one embodiment the active compound is a nerve impulseinhibitor. Suitable nerve impulse inhibitors for use in the buccalsprays of the invention include, but are not limited to,levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol,rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium,mivacurium, pancuronium, vercuronium, pipecuronium, and rocuronium.

[0037] In one embodiment the active compound is an anti-cholinergic.Suitable anti-cholinergics for use in the buccal sprays of the inventioninclude, but are not limited to, amantadine, ipratropium, oxitropium,and dicycloverine.

[0038] In one embodiment the active compound is an anti-convulsant.Suitable anti-convulsants for use in the buccal sprays of the inventioninclude, but are not limited to, acetazolamide, carbamazepine,clonazepam, diazepam, divalproex (valproic acid), ethosuximide,lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital,phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate,vigabatrin, and zonisamide.

[0039] In one embodiment the active compound is an anti-psychotic.Suitable anti-psychotics for use in the buccal sprays of the inventioninclude, but are not limited to, amisulpride, aripiprazole bifemelane,bromperidol, clozapine, chlorpromazine, haloperidol, iloperidoneloperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone,thiothixene, thioridazine, sulpride, and ziprasidone,

[0040] In one embodiment the active compound is an anxiolytic agent.Suitable anxiolytic agents for use in the buccal sprays of the inventioninclude, but are not limited to, amitryptiline, atracurium, buspirone,chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone,esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide,zaleplon, and zopiclone.

[0041] In one embodiment the active compound is a dopamine metabolisminhibitor. Suitable dopamine metabolism inhibitors for use in the buccalsprays of the invention include, but are not limited to, entacapone,lazebemide, selegiline, and tolcapone.

[0042] In one embodiment the active compound is an agent to treat poststroke sequelae. Suitable agents to treat post stroke sequelae for usein the buccal sprays of the invention include, but are not limited to,glatiramer, interferon beta 1A, interferon beta 1B, estradiol, andprogesterone.

[0043] In one embodiment the active compound is a neuroprotectant.Suitable neuroprotectants for use in the buccal sprays of the inventioninclude, but are not limited to, donepezil, memanine, nimodipine,riluzole, rivastigmine, tacrine, TAK147, and xaliproden.

[0044] In one embodiment the active compound is an agent to treatAlzheimer's disease. Suitable agents to treat Alzheimer's disease foruse in the buccal sprays of the invention include, but are not limitedto, carbidopa, levodopa, tacrine, donezepil, rivastigmine, andgalantamine.

[0045] In one embodiment the active compound is a neurotransmitter.Suitable neurotransmitters for use in the buccal sprays of the inventioninclude, but are not limited to, acetylcholine, serotonin,5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine,histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, andnitric oxide.

[0046] In one embodiment the active compound is a neurotransmitteragonist. Suitable neurotransmitter agonists for use in the buccal spraysof the invention include, but are not limited to, almotriptan,aniracetam, atomoxetine, benserazide, bromocriptine, bupropion,cabergoline, citalopram, clomipramine, desipramine, diazepam,dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram,fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan,nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline,paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline,sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, andzolmitriptan.

[0047] In one embodiment the active compound is a sedative. Suitablesedatives for use in the buccal sprays of the invention include, but arenot limited to, dexmedetomidine, eszopiclone, indiplon, zolpidem, andzaleplon.

[0048] In one embodiment the active compound is an agent for treatingattention deficit disorder. Suitable agents for treating attentiondeficit disorder for use in the buccal sprays of the invention include,but are not limited to, amphetamine, dextroamphetamine, methylphenidate,and pemoline.

[0049] In one embodiment the active compound is an agent for treatingnarcolepsy. Suitable agents for treating narcolepsy for use in thebuccal sprays of the invention include, but are not limited to,modafinil and mazindol.

[0050] In one embodiment the active compound is a central adregenicantagonists. A suitable central adregenic antagonists for use in thebuccal sprays of the invention includes, but is not limited to,mesoridazine.

[0051] In one embodiment the active compound is an anti-depressionagent. Suitable anti-depression agents for use in the buccal sprays ofthe invention include, but are not limited to, amitriptyline, amoxapine,bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin,fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine,nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline,sertraline, tranylcypromine, trazodone, and venlafaxine.

[0052] In one embodiment the active compound is an agent for treatingParkinson's disease. Suitable agents for treating Parkinson's diseasefor use in the buccal sprays of the invention include, but are notlimited to, amantadine, bromocriptine, carvidopa, levodopa, pergolide,and selegiline.

[0053] In one embodiment the active compound is a benzodiazepineantagonist. A suitable benzodiazepine antagonist for use in the buccalsprays of the invention includes, but is not limited to, flumazenil.

[0054] In one embodiment the active compound is a neurotransmitterantagonist. A suitable neurotransmitter antagonist for use in the buccalsprays of the invention includes, but is not limited, to deramciclane.

[0055] In one embodiment the active compound is a stimulant. Suitablestimulants for use in the buccal sprays of the invention include, butare not limited to, amphetamine, dextroamphetamine, dinoprostone,methylphenidate, methylphenidate, modafinil, and pemoline.

[0056] In one embodiment the active compound is a tranquilizer. Asuitable tranquilizer for use in the buccal sprays of the inventionincludes, but is not limited to, mesoridazine.

[0057] The formulations of the present invention comprise an activecompound or a pharmaceutically acceptable salt thereof. The term“pharmaceutically acceptable salts” refers to salts prepared frompharmaceutically acceptable non-toxic acids or bases including organicand inorganic acids or bases.

[0058] When an active compound of the present invention is acidic, saltsmay be prepared from pharmaceutically acceptable non-toxic bases. Saltsderived from all stable forms of inorganic bases include aluminum,ammonium, calcium, copper, iron, lithium, magnesium, manganese,potassium, sodium, zinc, etc. Particularly preferred are the ammonium,calcium, magnesium, potassium, and sodium salts. Salts derived frompharmaceutically acceptable organic non-toxic bases include salts ofprimary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines and basicion-exchange resins such as arginine, betaine, caffeine, choline, N,Ndibenzylethylenediamine, diethylamine, 2-diethylaminoethanol,2-dimethyl-aminoethanol, ethanolamine, ethylenediamine,N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine,isopropylamine, lysine, methyl-glucosamine, morpholine, piperazine,piperidine, polyamine resins, procaine, purine, theobromine,triethylamine, trimethylamine, tripropylamine, etc.

[0059] When an active compound of the present invention is basic, saltsmay be prepared from pharmaceutically acceptable non-toxic acids. Suchacids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric,ethane-sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric,isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric,pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric,p-toluenesulfonic, etc. Particularly preferred are citric, hydrobromic,maleic, phosphoric, sulfuric, and tartaric acids.

[0060] In the discussion of methods of treatment herein, reference tothe active compounds is meant to also include the pharmaceuticallyacceptable salts thereof. While certain formulations are set forthherein, the actual amounts to be administered to the mammal or man inneed of same are to be determined by the treating physician.

[0061] The invention is further defined by reference to the followingexamples, which are intended to be illustrative and not limiting.

[0062] The following are examples of certain classes. All values unlessotherwise specified are in weight percent.

EXAMPLES Example 1

[0063] Biologically Active Peptides Including Peptide Hormones A.Cyclosporine lingual spray Amounts preferred amount most preferredamount cyclosporine  5-50 10-35 15-25 water  5-20 7.5-50  9.5-12 ethanol  5-60 7.5-50  10-20 polyethylene 20-60 30-45 35-40 glycolflavors 0.1-5   1-4 2-3 B. Cyclosporine Non-Polar lingual spray Amountspreferred amount most preferred amount cyclosporine  1-50  3-40  5-30Migylol 20 25 30-40 Poly- 20 25 30-40 oxyethylated castor oil Butane25-80 30-70 33-50 flavors 0.1-5   1-4 2-3 C. Cyclosporine non-polar bitecaosule Amounts preferred amount most preferred amount cyclosporine 1-35  5-25 10-20 olive oil 25-60 35-55 30-45 poly- 25-60 35-55 30-45oxyethylated oleic glycerides flavors 0.1-5   1-4 2-3 D. Cyclosporinebite capsule Amounts preferred amount most preferred amount cyclosporine 5-50 10-35 15-25 polyethylene 20-60 30-45 35-40 glycol glycerin  5-307.5-25  10-20 propylene  5-30 7.5-25  10-20 glycol flavors 0.1-10  1-83-6 E. Sermorelin (as the acetate) lingual spray Amounts preferredamount most preferred sermorelin (as .01-5   .1-3   .2-1.0 the acetate)mannitol  1-25  5-20 10-15 monobasic 0.1-5    1-31  .5-2.5 sodiumphosphate, dibasic sodium 0.01-5   .05-3   0.1-0.5 phosphate waterethanol  5-30 7.5-25  9.5-15  polyethylene 20-60 30-45 35-40 glycolpropylene  5-25 10-20 12-17 glycol flavors 0.1-5   1-4 2-3 F. Octreotideacetate (Sandostatin) lingual spray Amounts preferred amount mostpreferred amount octreotide 0.001-0.5  0.005-0.250 0.01-0.10 acetateacetic acid  1-10 2-8 4-6 sodium acetate  1-10 2-8 4-6 sodium  3-30 .5-25 15-20 chloride flavors 0.1-5   0.5-.4  2-3 ethanol  5-30 7.5-20 9.5-15  water 15-95 35-90 65-85 flavors 0.1-5   1-4 2-3 G.Calcitonin-salmon lingual spray Amounts preferred amount most preferredamount calcitonin- 0.001-5    0.005-2     01-1.5 salmon ethanol  2-15 3-10   7-9.5 water 30-95 50-90 60-80 polyethylene  2-15  3-10   7-9.5glycol sodium 2.5-20   5-15   10-12.5 chloride flavors 0.1-5   1-4 2-3H. Insulin lispro, lingual spray Amounts preferred amount most preferredamount insulin 20-60  4-55  5-50 glycerin 0.1-10  0.25-5   0.1-1.5dibasic sodium  1-15 2.5-10  4-8 phosphate m-cresol,  1-25  5-25 7.5-12.5 zinc oxide 0.01-0.25   .05-0.15 0.075-0.10  m-cresol 0.1-1  0.2-0.8 0.4-0.6 phenol trace trace amounts trace amounts amounts ethanol 5-20 7.5-15   9-12 water 30-90 40-80 50-75 propylene  5-20 7.5-15  9-12 glycol flavors 0.1-5   0.5-3   0.75-2   adjust pH to 7.0-7.8 withHCI or NaOH

Example 2

[0064] CNS active amines and their salts: including but not limited totricyclic amines, GABA analogues, thiazides, phenothiazine derivatives,serotonin antagonists and serotonin reuptake inhibitors A. Sumatriptansuccinate lingual spray Amounts preferred amount most preferred amountsumatriptan 0.5-30  1-20 10-15 succinate ethanol  5-60 7.5-50  10-20propylene  5-30 7.5-20  10-15 glycol polyethylene  0-60 30-45 35-40glycol water  5-30 7.5-20  10-15 flavors 0.1-5   1-4 2-3 B. Sumatriptansuccinate bite capsule Amounts preferred amount most preferred amountsumatriptan 0.01-5   0.05-3.5  0.075-1.75  succinate polyethylene 25-7030-60 35-50 glycol glycerin 25-70 30-60 35-50 flavors 0.1-10  1-8 3-6 C.Clozepine lingual spray Amounts preferred amount most preferred amountclozepine 0.5-30   1-20 10-15 ethanol  5-60 7.5-50  10-20 propylene 5-30 7.5-20  10-15 glycol polyethylene  0-60 30-45 35-40 glycol water 5-30 7.5-20  10-15 flavors 0.1-5   1-4 2-3 D. Clozepine non-polarlinaual spray with propellant Amounts preferred amount most preferredamount clozepine 0.5-30   1-20 10-15 Migylol 20-85 25-70 30-40 Butanol 5-80 30-75 60-70 flavors 0.1-5   1-4 2-3 E. Clozepine non-polar lingualspray without propellant Amounts preferred amount most preferred amountclozepine 0.5-30   1-20 10-15 Migylol   70-99.5 80-99 85-90 flavors0.1-5   1-4 2-3 F. Cyclobenzaprine non-polar lingual spray Amountspreferred amount most preferred amount cyclobenzaprine 0.5-30   1-2010-15 (base) Migylol 20-85 25-70 30-40 Iso-butane 15-80 30-75 60-70flavors 0.1-5   1-4 2-3 G. Dexfenflurarnine hydrochloride lingual sprayAmounts preferred amount most preferred amount dexfenfluramine  5-307.5-20  10-15 Hcl ethanol  5-60 7.5-50  10-20 propylene  5-30 7.5-20 10-15 glycol polyethylene  0-60 30-45 35-40 glycol water  5-30 7.5-20 10-15 flavors 0.1-5   1-4 2-3

Example 3 Sulfonylureas

[0065] A. Glyburide lingual spray Amounts preferred amount mostpreferred amount glyburide 0.25-25   0.5-20  0.75-15   ethanol  5-60−7.5-50   10-20 propylene  5-30 7.5-20  10-15 glycol polyethylene  0-6030-45 35-40 glycol water 2.5-30   5-20  6-15 flavors 0.1-5   1-4 2-3 B.Glyburide non-polar bite capsule Amounts preferred amount most preferredamount glyburide 0.01-10   0.025-7.5  0.1-4   olive oil 30-60 35-5530-50 polyoxyethylated oleic glycerides 30-60 35-55 30-50 flavors0.1-5   1-4 2-3

Example 4 Antibiotics Anti-fungals and Anti-virals

[0066] A. Zidovudine [formerly called azidothymidine (AZT) (Retrovir)]non- polar lingual spray Amounts preferred amount most preferred amountzidovudine 10-50 15-40 25-35 Soya oil 20-85 25-70 30-40 Butane 15-8030-75 60-70 flavors 0.1-5   1-4 2-3 B. Erythromycin bite capsule bitecapsule Amounts preferred amount most preferred amount erythromycin25-65 30-50 35-45 polyoxyethylene  5-70 30-60 45-55 glycol glycerin 5-20 7.5-15    10-12.5 flavors  1-10 2-8 3-6 C. Ciprofloxacinhydrochloride bite capsule Amounts preferred amount most preferredamount ciprofloxacin 25-65 35-55 40-50 hydrochloride glycerin  5-207.5-15    10-12.5 polyethylene 120-75  30-65 40-60 glycol flavors  1-102-8 3-6 D. zidovudine [formerly called azidothymidine (AZT) (Retrovir]lingual spray Amounts preferred amount most preferred amount zidovudine10-50 15-40 25-35 water 30-80 40-75 45-70 ethanol  5-20 7.5-15  9.5-12.5 polyethylene  5-20 7.5-15   9.5-12.5 glycol flavors 0.1-5  1-4 2-3

Example 5

[0067] Anti-Emetics A. Ondansetron hydrochloride lingual spray Amountspreferred amount most preferred amount ondansetron  1-25  2-20 2.5-15 hydrochloride citric acid  1-10 2-8 2.5-5   monohydrate sodium citrate0.5-5   1-4 1.25-2.5  dihydrate water  1-90  5-85 10-75 ethanol  5-307.5-20  9.5-15  propylene  5-30 7.5-20  9.5-15  glycol polyethylene 5-30 7.5-20  9.5-15  glycol flavors  1-10 3-8   5-7.5 B. Dimenhydrinatebite capsule Amounts preferred amount most preferred amountdimenhydrinate 0.5-30   2-25  3-15 glycerin  5-20 7.5-15    10-12.5polyethylene 45-95 50-90 55-85 glycol flavors  1-10 2-8 3-6 C.Dimenhydrinate polar lingual spray Amounts preferred amount mostpreferred amount dimenhydrinate  3-50  4-40  5-35 water  5-90 10-8015-75 ethanol  1-80  3-50  5-10 polyethylene  1-80  3-50  5-15 glycolsorbitol 0.1-5   0.2-40  0.4-1.0 aspartame 0.01-0.5  0.02-0.4  0.04-0.1 flavors 0.1-5   1-4 2-3

Example 6

[0068] Histamine H-2 Receptor Antagonists A. Cimetidine hydrochloridebite capsule Amounts preferred amount most preferred amount cimetidineHCl 10-60 15-55 25-50 glycerin  5-20 7.5-15    10-12.5 polyethylene20-90 25-85 30-75 glycol flavors  1-10 2-8 3-6 B. Famotidine lingualspray Amounts preferred amount most preferred amount famotidine  1-35 5-30  7-20 water 2.5-25   3-20  5-10 L-aspartic 0.1-20   1-15  5-10acid polyethylene 20-97 30-95 50-85 glycol flavors 0.1-10    1-7.5 2-5C. Famotidine non-polar lingual spray Amounts preferred amount mostpreferred amount famotidine  1-35  5-30  7-20 Soya oil 10-50 15-40 15-20Butanel  5-80 30-75 45-70 poly- 10-50 15-40 15-20 oxyethylated oleicglycerides flavors 0.1-5   1-4 2-3

Example 7 Barbiturates

[0069] A. Phenytoin sodium lingual spray Amounts preferred amount mostpreferred amount phenytoin 10-60 15-55 20-40 sodium water 2.5-25   3-20 5-10 ethanol  5-30 7.5-20  9.5-15  propylene  5-30 7.5-20  9.5-15 glycol polyethylene  5-30 7.5-20  9.5-15  glycol flavors  1-10 3-8  5-7.5 B. Phenytoin non-polar lingual spray Amounts preferred amountmost preferred amount phenytoin  5-45 10-40 15-35 migylol 10-50 15-4015-20 Butane 15-80 30-75 60-70 polyoxyethylated 10-50 15-40 15-20 oleicglycerides flavors 0.1-10  1-8   5-7.5

Example 8 Prostaglandins

[0070] A. Carboprost thromethamine lingual spray Amounts preferredamount most preferred amount carboprost 0.05-5   0.1-3   0.25-2.5 thromethamine water 50-95 60-80 65-75 ethanol  5-20 7.5-15   9.5-12.5polyethylene  5-20 7.5-15   9.5-12.5 glycol sodium chloride  1-20  3-154-8 flavors 0.1-5   1-4 2-3 pH is adjusted with sodium hydroxide and/orhydrochloric acid B. Carboprost non-polar lingual spray Amountspreferred amount most preferred amount carboprost 0.05-5   0.1-3  0.25-2.5  migylol 25-50 30-45 35-40 Butane  5-60 10-50 20-35polyoxyethylated 25-50 30-45 35-40 oleic glycerides flavors 0.1-10  1-8  5-7.5

Example 9 Neutraceuticals

[0071] A. Carnitine as bite capsule (contents are a pastel Amountspreferred amount most preferred amount camitine  6-80 30-70 45-65fumarate soya oil 7.5-50  10-40 12.5-35 soya lecithin 0.001- 0.005-0.5 .01-0.1 1.0  Soya fats 7.5-50  10-40 12.5-35   flavors  1-10 2-8 3-6 B.Valerian as lingual spray Amounts preferred amount most preferred amountvalerian extract 0.1-10  0.2-7   0.25-5   water 50-95 60-80 65-75ethanol  5-20 7.5-15   9.5-12.5 polyethylene  5-20 7.5-15   9.5-12.5glycol flavors  1-10 2-8 3-6 C. Echinacea as bite capsule Amountspreferred amount most preferred amount echinacea 30-85 40-75 45-55extract soya oil 7.5-50  10-40 12.5-35   soya lecithin 0.001- 0.005-0.5 .01-0.1 1.0  Soya fats 7.5-50  10-40 12.5-35   flavors  1-10 2-8 3-6 D.Mixtures of ingredients Amounts preferred amount most preferred amountmagnesium oxide 15-40 20-35 25-30 chromium 0.01-1.0  0.02-0.5  .025-0.75picolinate folic acid .025-3.0  0.05-2.0  0.25-0.5  vitamin B-120.01-1.0  0.02-0.5  .025-0.75 vitamin E 15-40 20-35 25-30 Soya oil 10-4012.5-35 12 15-20 soya lecithin 0.1-5   0.2-4   0.5-1.5 soya fat 10-4015-35 17.5-20  

Example 10 Sleep Inducers (Also CNS Active Amine)

[0072] A. Diphenhydramine hydrochloride lingual spray Amounts preferredamount most preferred amount diphenhydramine   3-50.  4-40  5-35 HClwater  5-90 10-80 50-75 ethanol  1-80  3-50  5-10 polyethylene  1-80 3-50  5-15 glycol Sorbitol 0.1-5   0.2-4   0.4-1.0 aspartame 0.01-0.5 0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3

Example 11 Anti-asthmatics-bronchodilators

[0073] A. Isoproterenol Hydrochloride as polar lingual spray Amountspreferred amount most preferred amount isoproterenol 0.1-10  0.2-7.50.5-6   Hydrochloride water  5-90 10-80 50-75 ethanol  1-80  3-50  5-10polyethylene  1-80  3-50  5-15 glycol Sorbitol 0.1-5   0.2-4   0.4-1.0aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3 B.Terbutaline sulfate as polar lingual spray Amounts preferred amount mostpreferred amount terbutaline 0.1-10  0.2-7.5 0.5-6   sulfate water  5-9010-80 50-75 ethanol  1-10 2-8 2.5-5   Sorbitol 0.1-5   0.2-4   0.4-1.0aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3 C.Terbutaline as non-polar lingual spray Amounts preferred amount mostpreferred amount terbutaline 0.1-10  0.2-7.5 0.5-6   migylol 25-50 30-4535-40 isobutane  5-60 10-50 20-35 polyoxyethylated 25-50 30-45 35-40oleic glycerides flavors 0.1-10  1-8   5-7.5 D. Theophylline polar bitecapsule Amounts preferred amount most preferred amount theophylline 5-50 10-40 15-30 polyethylene 20-60 25-50 30-40 glycol glycerin 25-5035-45 30-40 propylene 25-50 35-45 30-40 glycol flavors 0.1-5   1-4 2-3E. Albuterol sulfate as polar lingual spray Amounts preferred amountmost preferred amount albuterol 0.1-10  0.2-7.5 0.5-6   sulfate water 5-90 10-80 50-75 ethanol  1-10 2-8 2.5-5   Sorbitol 0.1-5   0.2-4  0.4-1.0 aspartame 0.01-0.5  0.02-0.4  0.04-0.1  flavors 0.1-5   1-4 2-3

Example 12

[0074] Polar Solvent Formulations Using a Propellant: A. SulfonylureaAmount Preferred Amount Most-Preferred Amount glyburide 0.1-25% 0.5-15%  0.6-10%  Ethanol 40-99% 60-97% 70-97% Water 0.01- 0.1-4%  0.2-2%    5% Flavors 0.05- 0.1-5%   0.1-2.5% 10% Propellant  2-10% 3-5%3-4% B. Prostaglandin E (vasodilator) Amount Preferred AmountMost-Preferred Amount prostaglandin 0.01- 0.1-5%   0.2-3%   E₁ 10%Ethanol 10-90% 20-75% 25-50% Propylene  1-90%  5-80% 10-75% glycol Water0.01- 0.1-4%   0.2-2%    5% Flavors 0.05- 0.1-5%   0.1-2.5% 10%Propellant  2-10% 3-5% 3-4% C. Promethazine (antiemetic, sleep inducer,and CNS active amine) Amount Preferred Amount Most-Preferred Amountpromethazine  1-25%  3-15%  5-12% Ethanol 10-90% 20-75% 25-50% Propylene 1-90%  5-80% 10-75% glycol Water 0.01- 0.1-4%   0.2-2%    5% Flavors0.05- 0.1-5%   0.1-2.5% 10% Propellant  2-10% 3-5% 3-4% D. MeclizineAmount Preferred Amount Most-Preferred Amount meclizine  1-25%  3-15% 5-12% Ethanol  1-15%  2-10% 3-6  Propylene 20-98%  5-90% 10-85% glycolWater 0.01- 0.1-4%   0.2-2%    5% Flavors 0.05- 0.1-5%   0.1-2.5% 10%Propellant  2-10% 3-5% 3-4%

What is claimed is:
 1. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount of between 0.001 and 60 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof, and a polar solvent in an amount between 30 and 99 percent by weight of the total composition.
 2. The composition of claim 1, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
 3. The composition of claim 2, wherein the polar solvent is present in an amount between 37 and 98 percent by weight of the total composition, the active compound is present in an amount between 0.005 and 55 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.5 and 8 percent by weight of the total composition.
 4. The composition of claim 3, wherein the polar solvent is present in an amount between 60 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.01 and 40 percent by weight of the total composition, and the flavoring agent is present in an amount between 0.75 and 7.5 percent by weight of the total composition.
 5. The composition of claim 1, wherein the polar solvent is selected from the group consisting of polyethylene glycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.
 6. The composition of claim 1, wherein the polar solvent comprises aqueous polyethylene glycol.
 7. The composition of claim 1, wherein the polar solvent comprises aqueous ethanol.
 8. The composition of claim 1, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
 9. The composition of claim 1, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
 10. The composition of claim 1, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
 11. The composition of claim 1, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
 12. The composition of claim 1, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
 13. The composition of claim 1, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
 14. The composition of claim 1, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
 15. The composition of claim 1, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
 16. The composition of claim 1, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
 17. The composition of claim 1, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
 18. The composition of claim 1, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
 19. The composition of claim 1, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
 20. The composition of claim 1, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
 21. The composition of claim 1, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
 22. The composition of claim 1, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
 23. The composition of claim 1, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
 24. The composition of claim 1, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
 25. The composition of claim 1, wherein the active compound is the benzodiazepine antagonist flumazenil.
 26. The composition of claim 1, wherein the active compound is the neurotransmitter antagonist deramciclane.
 27. The composition of claim 1, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
 28. The composition of claim 1, wherein the active compound is the tranquilizer mesoridazine.
 29. The composition of claim 2, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 30. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 1. 31. The method of claim 30, wherein the amount of the spray is predetermined.
 32. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount of between 0.1 and 25 percent by weight of the total composition selected from the group consisting of consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; a polar solvent in an amount between 10 and 97 percent by weight of the total composition; and a propellant in an amount between 2 and 10 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or branched configuration.
 33. The composition of claim 32, further comprising a flavoring agent in an amount between 0.05 and 10 percent by weight of the total composition.
 34. The composition of claim 33, wherein the polar solvent is present in an amount between 20 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.1 and 15 percent by weight of the total composition, the propellant is present in an amount between 2 and 5 percent by weight of the composition, and the flavoring agent is present in an amount between 0.1 and 5 percent by weight of the total composition.
 35. The composition of claim 34, wherein the polar solvent is present in an amount between 25 and 97 percent by weight of the total composition, the active compound is present in an amount between 0.2 and 25 percent by weight of the total composition, the propellant is present in an amount between 2 and 4 percent by weight of the composition, and flavoring agent is present in an amount between 0.1 and 2.5 percent by weight of the total composition.
 36. The composition of claim 32, wherein the polar solvent is selected from the group consisting of polyethyleneglycols having a molecular weight between 400 and 1000, C₂ to C₈ mono- and poly-alcohols, and C₇ to C₁₈ alcohols of linear or branched configuration.
 37. The composition of claim 36, wherein the polar solvent comprises aqueous polyethylene glycol.
 38. The composition of claim 36, wherein the polar solvent comprises aqueous ethanol.
 39. The composition of claim 32, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
 40. The composition of claim 32, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
 41. The composition of claim 32, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
 42. The composition of claim 32, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
 43. The composition of claim 32, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
 44. The composition of claim 32, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
 45. The composition of claim 32, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
 46. The composition of claim 32, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
 47. The composition of claim 32, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
 48. The composition of claim 32, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
 49. The composition of claim 32, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
 50. The composition of claim 32, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
 51. The composition of claim 32, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
 52. The composition of claim 32, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
 53. The composition of claim 32, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
 54. The composition of claim 32, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
 55. The composition of claim 32, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
 56. The composition of claim 32, wherein the active compound is the benzodiazepine antagonist flumazenil.
 57. The composition of claim 32, wherein the active compound is the neurotransmitter antagonist deramciclane.
 58. The composition of claim 32, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
 59. The composition of claim 32, wherein the active compound is the tranquilizer mesoridazine.
 60. The composition of claim 32, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 61. The composition of claim 32, wherein the propellant is selected from the group consisting of propane, N-butane, iso-butane, N-pentane, iso-pentane, neo-pentane, and mixtures thereof.
 62. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 32. 63. The method of claim 62, wherein the amount of the spray is predetermined.
 64. A propellant free buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.005 and 55 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and a non-polar solvent in an amount between 30 and 99 percent by weight of the total composition.
 65. The composition of claim 64, further comprising a flavoring agent in an amount between 0.1 and 10 percent by weight of the total composition.
 66. The composition of claim 64, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
 67. The composition of claim 64, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
 68. The composition of claim 64, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
 69. The composition of claim 64, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
 70. The composition of claim 64, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
 71. The composition of claim 64, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
 72. The composition of claim 64, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
 73. The composition of claim 64, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
 74. The composition of claim 64, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
 75. The composition of claim 64, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
 76. The composition of claim 64, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
 77. The composition of claim 64, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
 78. The composition of claim 64, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
 79. The composition of claim 64, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
 80. The composition of claim 64, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
 81. The composition of claim 64, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
 82. The composition of claim 64, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
 83. The composition of claim 64, wherein the active compound is the benzodiazepine antagonist flumazenil.
 84. The composition of claim 64, wherein the active compound is the neurotransmitter antagonist deramciclane.
 85. The composition of claim 64, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
 86. The composition of claim 64, wherein the active compound is the tranquilizer mesoridazine.
 87. The composition of claim 65, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 88. The composition of claim 64, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.
 89. The composition of claim 88, wherein the solvent is miglyol.
 90. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 64. 91. The method of claim 90, wherein the amount of the spray is predetermined.
 92. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.05 and 50 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and a non-polar solvent in an amount between 19 and 85 percent by weight of the total composition; and a propellant in an amount between 5 and 80 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or brancehed configuration.
 93. The composition of claim 92, further comprising a flavoring agent in an amount of between 0.1 and 10 percent by weight of the total composition.
 94. The composition of claim 93, wherein the flavoring agent is selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners, and mixtures thereof.
 95. A buccal spray composition for transmucosal administration of a pharmacologically active compound comprising: an active compound in an amount between 0.01 and 40 percent by weight of the total composition selected from the group consisting of acetylcholinesterase inhibitors, nerve impulse inhibitors, anti-cholinergics, anti-convulsants, anti-psychotics, anxiolytic agents, dopamine metabolism inhibitors, agents to treat post stroke sequelae, neuroprotectants, agents to treat Alzheimer's disease, neurotransmitters, neurotransmitter agonists, sedatives, agents for treating attention deficit disorder, agents for treating narcolepsy, central adregenic antagonists, anti-depression agents, agents for treating Parkinson's disease, benzodiazepine antagonists, stimulants, neurotransmitter antagonists, tranquilizers, and mixtures thereof; and a non-polar solvent in an amount between 25 and 89 percent by weight of the total composition; a propellant in an amount between 10 and 70 percent by weight of the total composition, wherein said propellant is a C₃ to C₈ hydrocarbon of linear or brancehed configuration; and A flavoring agent is present in an amount between 1 and 8 percent by weight of the total composition.
 96. The composition of claim 95, wherein the propellant is present in an amount between 20 and 70 percent by weight of the total composition, the non-polar solvent is present in an amount between 25 and 75 percent by weight of the total composition, the active compound is present in an amount from between 0.25 and 35 percent by weight of the total composition, and the flavoring agent is present in an amount between 2 and 7.5 percent by weight of the total composition.
 97. The composition of claim 92, wherein the propellant is selected from the group consisting of propane, n-butane, iso-butane, n-pantane, iso-pentane, neo-pentane, and mixtures thereof.
 98. The composition of claim 97, wherein the propellant is n-butane or iso-butane and has a water content of not more than 0.2 percent and a concentration of oxidizing agents, reducing agents, Lewis acids, and Lewis bases of less than 0.1 percent.
 99. The composition of claim 92, wherein the solvent is selected from the group consisting of (C₂-C₂₄) fatty acid (C₂-C₆) esters, C₇-C₁₈ hydrocarbons of linear or branched configuration, C₂-C₆ alkanoyl esters, and triglycerides of C₂-C₆ carboxylic acids.
 100. The composition of claim 99, wherein the solvent is miglyol.
 101. The composition of claim 92, wherein the active compound is an acetylcholinesterase inhibitors selected from the group consisting of galantamine, neostigmine, physostigmine, and edrophonium, and mixtures thereof.
 102. The composition of claim 92, wherein the active compound is a nerve impulse inhibitor selected from the group consisting of levobupivacaine, lidocaine, prilocaine, mepivacaine, propofol, rapacuronium bromide, ropivacaine, tubocurarine, atracurium, doxaurium, mivacurium, pancuronium, vercuronium, pipecuronium, rocuronium, and mixtures thereof.
 103. The composition of claim 92, wherein the active compound is an anti-cholinergic selected from the group consisting of amantadine, ipratropium, oxitropium, dicycloverine, and mixtures thereof.
 104. The composition of claim 92, wherein the active compound is an anti-convulsant selected from the group consisting of acetazolamide, carbamazepine, clonazepam, diazepam, divalproex, ethosuximide, lamotrignine acid, levetriacetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, remacemide, trimethadione, topiramate, vigabatrin, zonisamide, and mixtures thereof.
 105. The composition of claim 92, wherein the active compound is an anti-psychotic selected from the group consisting of amisulpride, aripiprazole bifemelane, bromperidol, clozapine, chlorpromazine, haloperidol, iloperidone loperidone, olanzapine, quetiapine, fluphenazine, fumarate, risperidone, thiothixene, thioridazine, sulpride, ziprasidone, and mixtures thereof.
 106. The composition of claim 92, wherein the active compound is an anxiolytic agent selected from the group consisting of amitryptiline, atracurium, buspirone, chlorzoxazone, clorazepate, cisatracurium, cyclobenzaprine, eperisone, esopiclone, hydroxyzine, mirtazapine, mivacurium, pagoclone, sulperide, zaleplon, zopiclone, and mixtures thereof.
 107. The composition of claim 92, wherein the active compound is a dopamine metabolism inhibitor selected from the group consisting of entacapone, lazebemide, selegiline, tolcapone, and mixtures thereof.
 108. The composition of claim 92, wherein the active compound is an agent to treat post stroke sequelae selected from the group consisting of glatiramer, interferon beta 1A, interferon beta 1B, estradiol, progesterone, and mixtures thereof.
 109. The composition of claim 92, wherein the active compound is a neuroprotectant selected from the group consisting of donepezil, memanine, nimodipine, riluzole, rivastigmine, tacrine, TAK147, xaliproden, and mixtures thereof.
 110. The composition of claim 92, wherein the active compound is an agent to treat Alzheimer's disease selected from the group consisting of carbidopa, levodopa, tacrine, donezepil, rivastigmine, galantamine, and mixtures thereof.
 111. The composition of claim 92, wherein the active compound is a neurotransmitter selected from the group consisting of acetylcholine, serotonin, 5-hydroxytryptamine (5-HT), GABA, glutamate, aspartate, glycine, histamine, epinephrine, norpinephrine, dopamine, adenosine, ATP, nitric oxide, and mixtures thereof.
 112. The composition of claim 92, wherein the active compound is a neurotransmitter agonist selected from the group consisting of almotriptan, aniracetam, atomoxetine, benserazide, bromocriptine, bupropion, cabergoline, citalopram, clomipramine, desipramine, diazepam, dihydroergotamine, doxepin duloxetine, eletriptan, escitalopram, fluvoxamine, gabapentin, imipramine, moclobemide, naratriptan, nefazodone, nefiracetam acamprosate, nicergoline, nortryptiline, paroxetine, pergolide, pramipexole, rizatriptan, ropinirole, sertraline, sibutramine, sumatriptan, tiagabine, trazodone, venlafaxine, zolmitriptan, and mixtures thereof.
 113. The composition of claim 92, wherein the active compound is a sedative selected from the group consisting of dexmedetomidine, eszopiclone, indiplon, zolpidem, zaleplon, and mixtures thereof.
 114. The composition of claim 92, wherein the active compound is an agent for treating attention deficit disorder selected from the group consisting of amphetamine, dextroamphetamine, methylphenidate, pemoline, and mixtures thereof.
 115. The composition of claim 92, wherein the active compound is an agent for treating narcolepsy selected from the group consisting of modafinil, mazindol, and mixtures thereof.
 116. The composition of claim 92, wherein the active compound is an anti-depression agent selected from the group consisting of amitriptyline, amoxapine, bupropion, clomipramine, clomipramine, clorgyline, desipramine, doxepin, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, venlafaxine, and mixtures thereof.
 117. The composition of claim 92, wherein the active compound is an agent for treating Parkinson's disease selected from the group consisting of amantadine, bromocriptine, carvidopa, levodopa, pergolide, selegiline, and mixtures thereof.
 118. The composition of claim 92, wherein the active compound is the benzodiazepine antagonist flumazenil.
 119. The composition of claim 92, wherein the active compound is the neurotransmitter antagonist deramciclane.
 120. The composition of claim 92, wherein the active compound is a stimulant selected from the group consisting of amphetamine, dextroamphetamine, dinoprostone, methylphenidate, methylphenidate, modafinil, pemoline, and mixtures thereof.
 121. The composition of claim 92, wherein the active compound is the tranquilizer mesoridazine.
 122. A method of administering a pharmacologically active compound to a mammal comprising spraying the oral mucosa of the mammal with the composition of claim
 92. 123. The method of claim 122, wherein the amount of the spray is predetermined. 